SRPK3

Chr XX-linked

SRSF protein kinase 3

Also known as: MSSK-1, MSSK1, STK23, XLID114

NCBI Gene: 26576ENSG00000184343UniProt: Q9UPE1

This gene encodes a protein kinase similar to a protein kinase which is specific for the SR (serine/arginine-rich domain) family of splicing factors. A highly similar protein has been shown to play a role in muscle development in mice. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 114MIM #301134
X-linked
295
ClinVar variants
136
Pathogenic / LP
0.29
pLI score
0
Active trials
Clinical Summary— SRPK3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
136 Pathogenic / Likely Pathogenic· 138 VUS of 295 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.49LOEUF
pLI 0.292
Z-score 3.26
OE 0.24 (0.12–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.03Z-score
OE missense 0.99 (0.90–1.10)
262 obs / 263.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.12–0.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.90–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.38
0≤1.21.6
LoF obs/exp: 5 / 21.2Missense obs/exp: 262 / 263.4Syn Z: -3.23

ClinVar Variant Classifications

295 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic131
Likely Pathogenic5
VUS138
Likely Benign11
Benign6
Conflicting4
131
Pathogenic
5
Likely Pathogenic
138
VUS
11
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
128
0
131
Likely Pathogenic
1
0
4
0
5
VUS
8
109
21
0
138
Likely Benign
0
3
2
6
11
Benign
0
1
2
3
6
Conflicting
—4
Total101151579295

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SRPK3 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Intellectual developmental disorder, X-linked 114

MIM #301134

Molecular basis of disorder known

X-linked
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools